Dual-targeting organometallic ruthenium(II) anticancer complexes bearing EGFR-inhibiting 4-anilinoquinazoline ligands
文献类型：期刊论文
| 作者 | Zhang, Yang1,2; Zheng, Wei1,2; Luo, Qun1,2; Zhao, Yao1,2; Zhang, Erlong1,2,3; Liu, Suyan1,2; Wang, Fuyi1,2 |
| 刊名 | DALTON TRANSACTIONS
 |
| 出版日期 | 2015 |
| 卷号 | 44期号:29页码:13100-13111 |
| 英文摘要 | We have recently demonstrated that complexation with (eta(6)-arene)Ru-II fragments confers 4-anilinoquinazoline pharmacophores a higher potential for inducing cellular apoptosis while preserving the highly inhibitory activity of 4-anilinoquinazolines against EGFR and the reactivity of the ruthenium centre to 9-ethylguanine (Chem. Commun., 2013, 49, 10224-10226). Reported herein are the synthesis, characterisation and evaluation of the biological activity of a new series of ruthenium(II) complexes of the type [(eta(6)-arene)Ru(N,N-L)Cl]PF6 (arene = p-cymene, benzene, 2-phenylethanol or indane, L = 4-anilinoquinazolines). These organometallic ruthenium complexes undergo fast hydrolysis in aqueous solution. Intriguingly, the ligation of (arene)Ru-II fragments with 4-anilinoquinazolines not only makes the target complexes excellent EGFR inhibitors, but also confers the complexes high affinity to bind to DNA minor grooves while maintaining their reactivity towards DNA bases, characterising them with dual-targeting properties. Molecular modelling studies reveal that the hydrolysis of these complexes is a favourable process which increases the affinity of the target complexes to bind to EGFR and DNA. In vitro biological activity assays show that most of this group of ruthenium complexes are selectively active inhibiting the EGF-stimulated growth of the HeLa cervical cancer cell line, and the most active complex [(eta(6)-arene)Ru(N,N-L13)Cl]PF6 (4, IC50 = 1.36 mu M, L13 = 4-(3'-chloro-4'-fluoroanilino)-6-(2-(2-aminoethyl)aminoethoxy)-7-methoxyquinazoline) is 29-fold more active than its analogue, [(eta(6)-arene)Ru(N,N-ethylenediamine)Cl]PF6, and 21-fold more active than gefitinib, a well-known EGFR inhibitor in use clinically. These results highlight the strong promise to develop highly active ruthenium anticancer complexes by ligation of cytotoxic ruthenium pharmacophores with bioactive organic molecules. |
| 收录类别 | SCI |
| 语种 | 英语 |
| 公开日期 | 2016-05-09 |
| 源URL | [http://ir.iccas.ac.cn/handle/121111/27832]  |
| 专题 | 化学研究所_活体分析化学实验室 |
| 作者单位 | 1.Beijing Natl Lab Mol Sci, Beijing 100190, Peoples R China 2.Chinese Acad Sci, Inst Chem, CAS Key Lab Analyt Chem Living Biosyst, Beijing 100190, Peoples R China 3.Anhui Normal Univ, Coll Chem & Mat Sci, Key Lab Funct Mol Solids, Minist Educ,Anhui Lab Mol Based Mat, Wuhu 241000, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Yang,Zheng, Wei,Luo, Qun,et al. Dual-targeting organometallic ruthenium(II) anticancer complexes bearing EGFR-inhibiting 4-anilinoquinazoline ligands[J]. DALTON TRANSACTIONS,2015,44(29):13100-13111. |
| APA | Zhang, Yang.,Zheng, Wei.,Luo, Qun.,Zhao, Yao.,Zhang, Erlong.,...&Wang, Fuyi.(2015).Dual-targeting organometallic ruthenium(II) anticancer complexes bearing EGFR-inhibiting 4-anilinoquinazoline ligands.DALTON TRANSACTIONS,44(29),13100-13111. |
| MLA | Zhang, Yang,et al."Dual-targeting organometallic ruthenium(II) anticancer complexes bearing EGFR-inhibiting 4-anilinoquinazoline ligands".DALTON TRANSACTIONS 44.29(2015):13100-13111. |
入库方式： OAI收割
来源：化学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。